Reductively activated cleavage of DNA mediated by o,o '-diphenylenehalonium compounds

o,o'-Diphenylenehalonium (DPH) cations represent a novel class of DNA-affin ic compounds characterized by binding constants within the range of 10(5)-1 0(6) M-1. The maximum binding capacity of 2-2.5 base pairs per DPH cation a nd about 30% hypochromic reduction in the optical absorption of DPH cations upon binding to DNA suggest intercalation as a likely binding mode. In a D NA-bound form, DPH cations induce strand breaks upon reduction by radiation -produced electrons in aqueous solutions. In keeping with this mechanism, t he cleavage is strongly inhibited by oxygen and is not affected by OH radic al scavengers in the bulk. The yields of DPH-mediated base release signific antly exceed the yield of base release caused by hydroxyl radical (in the a bsence of scavenger) in anoxic solutions, The yields are weakly dependent o n DNA loading within the range from 5 to 50 base pairs per intercalator, wh ich indicates the ability of excess electrons in DNA to react with a scaven ger separated by tens of base pairs from the electron attachment site. The question regarding the mechanism by which the distant reactants reach each other in DNA remains unanswered, although it most likely involves electron hopping rather than a single-step long-distance tunneling. The latter concl usion is based on our finding that the electron affinity of DPR cations doe s not affect their properties as electron scavengers in DNA as would be exp ected if the direct long-distance tunneling is involved. (C) 2000 by Radiat ion Research Society.